PMID- 21518168
OWN - NLM
STAT- MEDLINE
DCOM- 20120315
LR  - 20221207
IS  - 1399-5448 (Electronic)
IS  - 1399-543X (Linking)
VI  - 12
IP  - 7
DP  - 2011 Nov
TI  - Preliminary studies related to anti-interleukin-1beta therapy in children with newly 
      diagnosed type 1 diabetes.
PG  - 656-67
LID - 10.1111/j.1399-5448.2011.00761.x [doi]
AB  - BACKGROUND: Interleukin-1beta (IL-1beta) may play a role in the pathogenesis of type 1 
      diabetes, but there are no data regarding the efficacy of agents antagonizing 
      IL-1beta in patients with this disorder. We characterized the effects of IL-1beta on 
      gene expression in peripheral blood mononuclear cells (PBMC) and the clinical and 
      gene expression effects of a short course of recombinant IL-1 receptor antagonist 
      protein, anakinra, on children with newly diagnosed diabetes. METHODS: PBMC from 
      healthy adult volunteers were exposed to IL-1beta for 24 h in vitro. Gene expression 
      was analyzed via microarray. Fifteen children within 1 wk of diagnosis of type 1 
      diabetes received daily anakinra for 28 d and were followed for 6 months. Blood 
      was drawn for microarray analysis before and after anakinra treatment. Insulin 
      secretory capacity was assessed by mixed-meal tolerance testing (MMTT) at 3-4 wk 
      and 7 months after diagnosis. Hemoglobin A1c (HbA1c) and insulin doses were 
      periodically recorded. Data were compared with two historical control groups of 
      children with newly diagnosed diabetes. RESULTS: Although in vitro exposure to 
      IL-1beta caused many changes in PBMC gene expression, gene expression did not change 
      significantly after anakinra therapy in diabetes patients. Anakinra-treated 
      patients had similar HbA1c and MMTT responses, but lower insulin requirements 1 
      and 4 months after diagnosis compared to controls, and lower 
      insulin-dose-adjusted A1c 1 month after diagnosis. CONCLUSIONS: Anakinra therapy 
      is well tolerated in children with newly diagnosed type 1 diabetes. Further 
      studies are needed to demonstrate biological effects.
CI  - (c) 2011 John Wiley & Sons A/S.
FAU - Sumpter, Kathryn M
AU  - Sumpter KM
AD  - Department of Pediatrics, University of Texas Southwestern Medical Center, 
      Dallas, TX, USA.
FAU - Adhikari, Soumya
AU  - Adhikari S
FAU - Grishman, Ellen K
AU  - Grishman EK
FAU - White, Perrin C
AU  - White PC
LA  - eng
GR  - UL1 RR024982/RR/NCRR NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110424
PL  - Denmark
TA  - Pediatr Diabetes
JT  - Pediatric diabetes
JID - 100939345
RN  - 0 (Antirheumatic Agents)
RN  - 0 (C-Peptide)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Interleukin 1 Receptor Antagonist Protein)
RN  - 0 (Interleukin-1beta)
RN  - 0 (hemoglobin A1c protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Antirheumatic Agents/*therapeutic use
MH  - Area Under Curve
MH  - C-Peptide/metabolism
MH  - Cells, Cultured
MH  - Child
MH  - Diabetes Mellitus, Type 1/*drug therapy/metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - Glycated Hemoglobin/metabolism
MH  - Humans
MH  - Hypoglycemic Agents/administration & dosage
MH  - Injections, Subcutaneous/adverse effects
MH  - Insulin/administration & dosage/metabolism
MH  - Insulin Secretion
MH  - Interleukin 1 Receptor Antagonist Protein/*therapeutic use
MH  - Interleukin-1beta/antagonists & inhibitors/*metabolism
MH  - Leukocytes, Mononuclear/*metabolism
MH  - Male
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pilot Projects
EDAT- 2011/04/27 06:00
MHDA- 2012/03/16 06:00
CRDT- 2011/04/27 06:00
PHST- 2011/04/27 06:00 [entrez]
PHST- 2011/04/27 06:00 [pubmed]
PHST- 2012/03/16 06:00 [medline]
AID - 10.1111/j.1399-5448.2011.00761.x [doi]
PST - ppublish
SO  - Pediatr Diabetes. 2011 Nov;12(7):656-67. doi: 10.1111/j.1399-5448.2011.00761.x. 
      Epub 2011 Apr 24.